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Progress toward the development of a viable BACE‐1 inhibitor
Author(s) -
Stachel Shawn J.
Publication year - 2009
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20289
Subject(s) - chemistry , amyloid precursor protein , peptidomimetic , catabolism , drug discovery , amyloid precursor protein secretase , extracellular , drug development , drug , pharmacology , cleavage (geology) , biochemistry , amyloid β , enzyme , alzheimer's disease , disease , biology , medicine , peptide , paleontology , fracture (geology)
Abstract Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive formation of insoluble amyloid plaque and fibrillary tangles. Plaques are extracellular constructs consisting primarily of Aβ 42 derived from the catabolism of β‐amyloid precursor protein (APP). β‐Secretase (BACE‐1) is the enzyme responsible for the initiatory cleavage event in APP catabolism. The central role of BACE‐1 in the production of Aβ 42 has made it an attractive target for drug development. However, the development of BACE‐1 inhibitors has been hampered by difficulty in identifying inhibitors with acceptable pharmacokinetic and CNS penetration properties. The maturation of the BACE‐1 drug discovery effort from typical peptidomimetic inhibitors to more novel structural classes is reviewed. Drug Dev Res 70, 2009. © 2009 Wiley‐Liss, Inc.